The objective of this proposal is to find leads for new compounds and develop the synthesis of second generation 99mTc radiopharmaceuticals as imaging drugs by constructing cold rhenium analogs based on the Re(CO)3+ fragment . The chemistry of rhenium is directly analogous to that of technetium, and can be used to optimize target compounds prior to generating the corresponding 99mTc radiopharmaceutical candidate. s will be achieved by: 1) exploring the fundamental aqueous chemistry of the Re(CO)3+ fragment, 2) synthesizing specific Re(CO)3+ complexes to generate bifunctional chelating agents (BFCAs), 3) evaluating lead candidates with cell line studies and 4) investigating the processing of Re(CO)3+ complexes in the cell. This work will be carried out primarily in the laboratories of Prof. Christopher J. Ziegler at the University of Akron, but significant assistance will come from Prof. Richard Herrick at the College of the Holy Cross, one of the collaborators in this proposal. PUBLIC HEALTH RELEVANCE: This work is relevant to public health in several ways. First, this research will directly contribute to the development of new technetium radiopharmaceuticals. Technetium-based imaging agents are the most common radionuclides in use in the clinic today, and are crucial for the imaging of brain, cardiovascular and skeletal tissues. In addition, this grant will assist in the training of both graduate and undergraduate students who will go on to work in health related professions.